Trials, Tribulations, and Trends in Tumor Modeling in Mice

Selection of mouse models of cancer is often based simply on availability of a mouse strain and a known compatible tumor. Frequently this results in use of tumor models long on history but short on homology and quality control. Other factors including genetics, sex, immunological status, method and site of tumor implantation, technical competence, biological activity of the tumor, protocol sequence and timing, and selection of endpoints interact to produce outcomes in tumor models. Common reliance on survival and tumor burden data in a single mouse model often skews expectations towards high remission and cure rates; a finding seldom duplicated in clinical trials. Inherent limitations of tumor models coupled with the advent of new therapeutic targets reinforce need for careful attention to design, conduct, and stringent selection of in vivo and ex vivo endpoints. Preclinical efficacy testing for anti-tumor therapies should progress through a series of models of increasing sophistication that includes incorporation of genetically engineered animals, and orthotopic and combination therapy models. Pharmacology and safety testing in tumor-bearing animals may also help to improve predictive value of these models for clinical efficacy. Trends in bioinformatics, genetic refinements, and specialized imaging techniques are helping to maintain mice as the most scientifically and economically powerful model of malignant neoplasms

Mycobacterium arupense sp. nov., a novel moderately growing nonchromogenic bacterium isolated from clinical specimens

ManuscriptThis author manuscript discusses how several isolates of Mycobacterium species related to the M. terrae complex have been isolated from clinical samples. In the clinical microbiology laboratory, partial 16S rRNA gene sequencing (approximate first 500 base pairs) is often used to identify Mycobacterium species rather than full 16S rRNA gene sequencing. Partial 16S rRNA gene sequence analysis revealed 100% identity between 65 clinical isolates and Mycobacterium species MCRO 6 (GenBank accession no. X93032). Even after sequencing the nearly full 16S rRNA gene, the closest match to an existing type strain is only 99.6% similar to M. nonchromogenicum (ATCC 19530T). Sequencing of the nearly full 16S rRNA gene, the 16S-23S internal transcribed spacer region, and the hsp65 gene did not reveal genotypic identity with the type strains of M. nonchromogenicum, M. terrae, or M. triviale

Effect of Combination Folic Acid, Vitamin B6 , and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial.

Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12 , B6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017 American Society for Bone and Mineral Research

Carotid thromboendarterectomy for recent total occlusion of the internal carotid artery

AbstractBackground: The efficacy of emergency carotid thromboendarterectomy (CTEA) for acute internal carotid artery (ICA) thrombosis has been questioned. We evaluated the use of CTEA in patients with recent ICA occlusion. Methods: From August 1989 to December 1999 patients who underwent urgent CTEA for recent ICA thrombosis were retrospectively evaluated. Patient data analyzed included age, sex, comorbid risk factors, diagnostic evaluation, operative procedure, and long-term follow-up with clinical assessment and carotid duplex scan. Neurologic status was evaluated with the Modified Rankin Scale (MRS) before the operation, immediately after the operation, and at 3- to 6-months' follow-up. Results: Twenty-nine patients underwent emergency ipsilateral CTEA for acute ICA thrombosis over the last 10 years. The average age of the patients was 69.9 ± 1.7 years, and 66% were men. Patient risk factors included diabetes (7 [24%]), hypertension (21 [72%]), coronary artery disease (8 [29%]), and history of tobacco abuse (20 [69%]). Presenting symptoms included cerebrovascular accident (7 [24%]), transient ischemic attack (nonamaurosis) (10 [34%]), crescendo transient ischemic attack (7 [24%]), stroke in evolution (2 [7%]), and amaurosis fugax (3 [10%]). Diagnostic evaluation included computed tomographic scan (29 [100%]), magnetic resonance imaging/magnetic resonance angiography (4 [14%]), duplex scan evaluation of the carotid arteries (23 [79%]), and cerebral angiography (18 [64%]). Antegrade flow in the ICA was successfully established in 24 (83%) of 29 patients and confirmed with intraoperative angiography or duplex sonography. Postoperative morbidity included 2 hematomas (7%), 4 transient cranial nerve deficits (14%), and 1 conversion to hemorrhagic stroke (3.6%), which resulted in the only death (3.6%). MRS scores averaged 3.4 ± 0.2 preoperatively. Follow-up averaging 74.1 ± 21 months (range, 3-140 months) was obtained in 27 (93%) patients. Improvement or deterioration was defined as a change in MRS ± 1. Immediately postoperatively, 14 (48%) patients were improved, 2 (7%) deteriorated, and 13 (45%) had no change. At 3 to 6 months, 20 (74%) of 27 patients were improved, seven (26%) had no change, and none deteriorated. Of patients with successful CTEA, 23 (96%) of 24 had a patent ICA on follow-up duplex scan evaluation, and there was no evidence of recurrent ipsilateral neurologic events at an average of 49 months. Conclusion: These data support an aggressive early surgical intervention for acute ICA thrombosis in carefully selected patients. In the previous decade we reported a 46% success rate for establishing antegrade flow in the ICA long term. Data from this decade show a 79% (P =.0114) success rate for establishing antegrade flow long term in all patients undergoing emergency CTEA. New and improved imaging modalities have allowed better patient selection, resulting in improved outcomes. (J Vasc Surg 2001;33:242-50.

Patient/Family Education for Newly Diagnosed Pediatric Oncology Patients

There is a paucity of data to support evidence-based practices in the provision of patient/family education in the context of a new childhood cancer diagnosis. Since the majority of children with cancer are treated on pediatric oncology clinical trials, lack of effective patient/family education has the potential to negatively affect both patient and clinical trial outcomes. The Children’s Oncology Group Nursing Discipline convened an interprofessional expert panel from within and beyond pediatric oncology to review available and emerging evidence and develop expert consensus recommendations regarding harmonization of patient/family education practices for newly diagnosed pediatric oncology patients across institutions. Five broad principles, with associated recommendations, were identified by the panel, including recognition that (1) in pediatric oncology, patient/family education is family-centered; (2) a diagnosis of childhood cancer is overwhelming and the family needs time to process the diagnosis and develop a plan for managing ongoing life demands before they can successfully learn to care for the child; (3) patient/family education should be an interprofessional endeavor with 3 key areas of focus: (a) diagnosis/treatment, (b) psychosocial coping, and (c) care of the child; (4) patient/family education should occur across the continuum of care; and (5) a supportive environment is necessary to optimize learning. Dissemination and implementation of these recommendations will set the stage for future studies that aim to develop evidence to inform best practices, and ultimately to establish the standard of care for effective patient/family education in pediatric oncology

Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events.

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women\u27s Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratioor =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL rati

\u3cem\u3eOAS1\u3c/em\u3e Polymorphisms Are Associated with Susceptibility to West Nile Encephalitis in Horses

West Nile virus, first identified within the United States in 1999, has since spread across the continental states and infected birds, humans and domestic animals, resulting in numerous deaths. Previous studies in mice identified the Oas1b gene, a member of the OAS/RNASEL innate immune system, as a determining factor for resistance to West Nile virus (WNV) infection. A recent case-control association study described mutations of human OAS1 associated with clinical susceptibility to WNV infection. Similar studies in horses, a particularly susceptible species, have been lacking, in part, because of the difficulty in collecting populations sufficiently homogenous in their infection and disease states. The equine OAS gene cluster most closely resembles the human cluster, with single copies of OAS1, OAS3 and OAS2 in the same orientation. With naturally occurring susceptible and resistant sub-populations to lethal West Nile encephalitis, we undertook a case-control association study to investigate whether, similar to humans (OAS1) and mice (Oas1b), equine OAS1 plays a role in resistance to severe WNV infection. We identified naturally occurring single nucleotide mutations in equine (Equus caballus) OAS1 and RNASEL genes and, using Fisher\u27s Exact test, we provide evidence that mutations in equine OAS1 contribute to host susceptibility. Virtually all of the associated OAS1 polymorphisms were located within the interferon-inducible promoter, suggesting that differences in OAS1 gene expression may determine the host\u27s ability to resist clinical manifestations associated with WNV infection

African American community, Rockingham County: an action-oriented community diagnosis: findings and next steps of action

In October 2007, a team of five graduate students from the University of North Carolina at Chapel Hill School of Public Health began an Action-Oriented Community Diagnosis (AOCD) with the African American community in Rockingham County. An AOCD is a community-based process by which the resources, strengths, needs, and challenges of a community are identified. After identification, the process transitions to generating dialogue and creating action steps to build on community strengths and address challenges. Guided by preceptors Debbie Mason of Rockingham County Healthy Carolinians and Katrina White of the Rockingham County Department of Public Health, the student team spent the next seven months attending community events, examining data about Rockingham County from websites and government documents, and conducting interviews and focus groups with both service providers and community members regarding community strengths and community challenges. After analyzing the responses, the team identified thirteen common themes. With the help of a community advisory committee (CAC), the team planned and held a public forum, “Community Dialogue for Change,” on April 14, 2008. The CAC selected five of the original thirteen themes for focused discussion at the forum based on their importance to the community and how easily they could be addressed. Five themes were chosen so that the five student team members could each lead a discussion group on one theme..At the forum, the team highlighted the community‟s strengths such as churches and spirituality, caring people, and leadership capacity as well as challenges related to the five themes chosen for discussion. The approximately 70 people in attendance broke into smaller discussion groups and generated action steps to address each theme. The following challenges and action steps were presented at the forum: Employment- The lack of job opportunities for African Americans within the county is a concern. This affects both adults who have lost jobs and youth seeking jobs. Develop a mentoring program that would place youth in government, corporate, and small business environments. Survey students to determine their career interests so that job fairs and career programs would be more appealing. Create a resource listing of employers willing to hire ex-offenders. Attitudes Towards Education- There is concern that education is not a priority in the county, as seen by high drop-out rates and not enough students going to college. Approach the school board about offering diversity training to teachers and other employees. Approach local colleges that train teachers about offering diversity training in their curricula. Guidance for Youth- Too many African American youth, especially young men, lack positive guidance for their futures. Set up a forum for youth-adult conversation as a starting point for better understanding. Use the media, church newsletters, and organizations to spread the word about the need to come together for better guidance for youth. Find out what mentoring programs churches currently have in place, and increase the number and quality of these programs. Include volunteering for school mentoring programs in regular church service projects, with an emphasis on peer mentors. Establish programs to re-train parents and include professionals in the community with different skill sets for parenting. Racial Discrimination- Community members noted various ways in which racial discrimination happens in the county, such as differences in pay, ability to get loans, and treatment of students. Create a forum to increase dialogue between parents of school children to address issues such as racial discrimination in schools. Increase parental and community involvement in volunteer opportunities in schools. Create guidelines for fair treatment of students for use by teachers and administrators. Preventive Health Care- Low use of preventive health care services for conditions such as diabetes and high blood pressure leads to an increased need for treatment and poor health. Form a group in charge of developing educational flyers with health messages to be placed in grocery stores, doctors‟ offices, daycares, churches, schools, and recreational facilities. This education campaign would also incorporate the use of nutritionists to develop health messages for church newsletters. Form a “take a friend to the doctor” program to assist those without their own personal transportation in getting to preventive health care appointments. This would build upon existing resources available in the community such as Caregivers of Rockingham County and Pelham Transportation in order to make transportation to medical appointments more convenient for community members. The purpose of this final report is to give the African American community of Rockingham County and other concerned individuals a tangible resource that presents the findings of the community assessment as well as a report of the discussions and action steps which emerged at the community forum. It is divided into six sections: Introduction; Background on Rockingham County; Primary Data Findings; Methods; The Forum; and Recommendations and Conclusions. This document should be a tool which all community members can continuously refer to as they address various challenges and work towards progress.Master of Public Healt